Characterizing natural hydrogel for reconstruction of three‐dimensional lymphoid stromal network to model T‐cell interactions

Abstract Hydrogels have been used in regenerative medicine because they provide a three‐dimensional environment similar to soft tissues, allow diffusion of nutrients, present critical biological signals, and degrade via endogenous enzymatic mechanisms. Herein, we developedin vitrosystem mimicking cell–cell and cell–matrix interactions in secondary lymphoid organs (SLOs). Existingin vitroculture systems cannot accurately represent the complex interactions happening between T‐cells and stromal cells in immune response. To model T‐cell interaction in SLOsin vitro, we encapsulated stromal cells in fibrin, collagen, or fibrin–collagen hydrogels and studied how different mechanical and biological properties affect stromal network formation. Overall, fibrin supplemented with aprotinin was superior to collagen and fibrin–collagen in terms of network formation and promotion of T‐cell penetration. After 8 days of culture, stromal networks formed through branching and joining with other adjacent cell populations. T‐cells added to the newly formed stromal networks migrated and attached to stromal cells, similar to the T‐cell zones of the lymph nodesin vivo. Our results suggest that the constructed three‐dimensional lymphoid stromal network can mimic thein vivoenvironment and allow the modeling of T‐cell interaction in SLOs. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 103A: 2701–2710, 2015.